TSPYL5 depletion induces specific death of ALT cells through USP7-dependent proteasomal degradation of POT1.
Open accessAbstract
A significant fraction (∼10%) of cancer cells maintain their telomere length via a telomerase-independent mechanism known as alternative lengthening of telomeres (ALT). There are no known molecular, ALT-specific, therapeutic targets. We have identified TSPYL5 (testis-specific Y-encoded-like protein 5) as a PML body component, co-localizing with ALT telomeres and critical for ALT+ cell viability. TSPYL5 was described as an inhibitor of the USP7 deubiquitinase. We report that TSPYL5 prevents the poly-ubiquitination of POT1-a shelterin component-and protects POT1 from proteasomal degradation exclusively in ALT+ cells. USP7 depletion rescued POT1 poly-ubiquitination and loss, suggesting that the deubiquitinase activates POT1 E3 ubiquitin ligase(s). Similarly, PML depletion suppressed POT1 poly-ubiquitination, suggesting an interplay between USP7 and PML to trigger POT1 degradation in TSPYL5-depleted ALT+ cells. We demonstrate that ALT telomeres need to be protected from POT1 degradation in ALT-associated PML bodies and identify TSPYL5 as an ALT+ cancer-specific therapeutic target.
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USP7 influences genome stability through maintenance of telomere ends.
“Another means by which USP7 influences genome stability, is through the maintenance of telomere ends (Figure 3D; Zemp and Lingner, 2014; Episkopou et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Episkopou et al., 2019
USP7 has an apparent protective role in telomerase+ cells via TPP1 stabilization.
“Indeed, while USP7 has an apparent protective role in telomerase+ cells – via TPP1 stabilization – USP7 seems to promote POT1 degradation in ALT+ cells (Episkopou et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Episkopou et al., 2019
USP7 is thought to contribute to POT1 degradation by stabilizing an E3 ubiquitin ligase that accumulates within PML bodies.
“Here, USP7 is thought to contribute to POT1 degradation by stabilizing one of the many E3 ubiquitin ligases known to accumulate within PML bodies (Cheng and Kao, 2013; Episkopou et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Episkopou et al., 2019
PML proteins are essential for USP7 to degrade POT1.
“USP7 also associates with PML bodies (Sarkari et al., 2011) and PML proteins are essential for USP7 to degrade POT1 (Episkopou et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Episkopou et al., 2019
TSPYL5 depletion causes cell death in ALT+ cells due to unrestricted POT1 degradation, unlike in telomerase+ cells.
“Regulation of USP7 by TSPYL5 is of particular importance in ALT+ cells, as unlike in telomerase+ cells, TSPYL5 depletion causes cell death due to unrestricted POT1 degradation (Episkopou et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Episkopou et al., 2019
USP7 seems to promote POT1 degradation in ALT+ cells.
“Indeed, while USP7 has an apparent protective role in telomerase+ cells – via TPP1 stabilization – USP7 seems to promote POT1 degradation in ALT+ cells (Episkopou et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Episkopou et al., 2019
USP7 localizes to telomere ends in both telomerase+ and ALT+ human cell lines.
“USP7 localizes to telomere ends in both telomerase+ and ALT+ human cell lines, however, its roles at either seem to differ.”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Episkopou et al., 2019
Cites
Shelterin: the protein complex that shapes and safeguards human telomeres
de Lange, T. (2005) · Genes & Development · doi:10.1101/gad.1346005 · Cited by 3,056 · see citing works
Alternative lengthening of telomeres: models, mechanisms and implications
Cesare, A. J., & Reddel, R. R. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2763 · Cited by 1,102 · see citing works
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., & de Lange, T. (1999) · Science · doi:10.1126/science.283.5406.1321 · Cited by 1,086 · see citing works
Méndez, J., & Stillman, B. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8602-8612.2000 · Cited by 922 · see citing works
Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1
Denchi, E. L., & de Lange, T. (2007) · Nature · doi:10.1038/nature06065 · Cited by 880 · see citing works
The POT1-TPP1 telomere complex is a telomerase processivity factor.
Wang, F., Podell, E. R., Zaug, A. J., Yang, Y., Baciu, P., Cech, T. R., & Lei, M. (2007) · Nature · doi:10.1038/nature05454 · Cited by 704 · see citing works
POT1 as a terminal transducer of TRF1 telomere length control
Loayza, D., & de Lange, T. (2003) · Nature · doi:10.1038/nature01688 · Cited by 696 · see citing works
A dynamic role of HAUSP in the p53-Mdm2 pathway
Li, M., Brooks, C. L., Kon, N., & Gu, W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00157-1 · Cited by 679 · see citing works
Purification of Proteins Associated with Specific Genomic Loci
Déjardin, J., & Kingston, R. E. (2009) · Cell · doi:10.1016/j.cell.2008.11.045 · Cited by 545 · see citing works
Characterization of NEDD8, a Developmentally Down-regulated Ubiquitin-like Protein
Kamitani, T., Kito, K., Nguyen, H. P., & Yeh, E. T. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28557 · Cited by 535 · see citing works
Ye, J. Z.-S., Hockemeyer, D., Krutchinsky, A. N., Loayza, D., Hooper, S. M., Chait, B. T., & de Lange, T. (2004) · Genes & Development · doi:10.1101/gad.1215404 · Cited by 459 · see citing works
PTOP interacts with POT1 and regulates its localization to telomeres
Liu, D., Safari, A., O'Connor, M. S., Chan, D. W., Laegeler, A., Qin, J., & Songyang, Z. (2004) · Nature Cell Biology · doi:10.1038/ncb1142 · Cited by 450 · see citing works
Potts, P. R., & Yu, H. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1259 · Cited by 401 · see citing works
A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis
Tefferi, A., Lasho, T. L., Begna, K. H., Patnaik, M. M., Zblewski, D., Finke, C. M., Laborde, R. R., Wassie, E. A., Schimek, L., Hanson, C. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1310523 · Cited by 324 · see citing works
Everett, R. D., Rechter, S., Papior, P., Tavalai, N., Stamminger, T., & Orr, A. (2006) · Journal of Virology · doi:10.1128/jvi.00734-06 · Cited by 323 · see citing works
TPP1 OB-Fold Domain Controls Telomere Maintenance by Recruiting Telomerase to Chromosome Ends
Zhong, F. L., Batista, L. F. Z., Freund, A., Pech, M. F., Venteicher, A. S., & Artandi, S. E. (2012) · Cell · doi:10.1016/j.cell.2012.07.012 · Cited by 308 · see citing works
Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1α
Arnoult, N., Beneden, A. V., & Decottignies, A. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2364 · Cited by 258 · see citing works
Self-citationCritical role for Daxx in regulating Mdm2
Tang, J., Qu, L., Zhang, J., Wang, W., Michaelson, J. S., Degenhardt, Y., El‐Deiry, W. S., & Yang, X. (2006) · Nature Cell Biology · doi:10.1038/ncb1442 · Cited by 239 · see citing works
Molecular mechanisms of activity and derepression of alternative lengthening of telomeres
Pickett, H. A., & Reddel, R. R. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3106 · Cited by 203 · see citing works
Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia
Baerlocher, G. M., Leibundgut, E. O., Ottmann, O. G., Spitzer, G., Odenike, O. M., McDevitt, M. A., Röth, A., Daskalakis, M., Burington, B. E., Stuart, M. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503479 · Cited by 199 · see citing works
Alternative Lengthening of Telomeres is characterized by reduced compaction of telomeric chromatin
Episkopou, H., Drašković, I., Beneden, A. V., Tilman, G., Mattiussi, M., Gobin, M., Arnoult, N., Londoño‐Vallejo, A., & Decottignies, A. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku114 · Cited by 192 · see citing works
Self-citationSystematic approaches to identify E3 ligase substrates
Iconomou, M., & Saunders, D. N. (2016) · Biochemical Journal · doi:10.1042/bcj20160719 · Cited by 179 · see citing works
Draskovic, I., Arnoult, N., Steiner, V., Bacchetti, S., Lomonte, P., & Londoño-Vallejo, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907689106 · Cited by 175 · see citing works
García-Expósito, L., Bournique, E., Bergoglio, V., Bose, A., González, J. B., Zhang, S., Roncaioli, J. L., Lee, M., Wallace, C. T., Watkins, S. C., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.048 · Cited by 148 · see citing works
Canning, M., Boutell, C., Parkinson, J., & Everett, R. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402885200 · Cited by 142 · see citing works
Boros, J., Arnoult, N., Stroobant, V., Collet, J., & Decottignies, A. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00205-14 · Cited by 135 · see citing works
Self-citationPoncet, D., Belleville, A., de Roodenbeke, C. T., de Climens, A. R., Simon, E. B., Merle‐Béral, H., Callet‐Bauchu, E., Salles, G. A., Sabatier, L., Delić, J., et al. (2007) · Blood · doi:10.1182/blood-2007-09-111245 · Cited by 132 · see citing works
TSPYL5 suppresses p53 levels and function by physical interaction with USP7.
Epping, M. T., Meijer, L. A. T., Krijgsman, O., Bos, J. L., Pandolfi, P. P., & Bernards, R. (2011) · Nature Cell Biology · doi:10.1038/ncb2142 · Cited by 117 · see citing works
Telomere Maintenance through Spatial Control of Telomeric Proteins
Chen, L., Liu, D., & Songyang, Z. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00603-07 · Cited by 117 · see citing works
Gallagher, W. M., Bergin, O. E., Rafferty, M., Kelly, Z. D., Nolan, I.-M., Fox, E., Culhane, A. C., McArdle, L., Fraga, M. F., Hughes, L., et al. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi152 · Cited by 116 · see citing works
Extensive Proliferation of Human Cancer Cells with Ever-Shorter Telomeres
Dagg, R. A., Pickett, H. A., Neumann, A. A., Napier, C. E., Henson, J. D., Teber, E., Arthur, J. W., Reynolds, C. P., Murray, J. E., Haber, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.087 · Cited by 109 · see citing works
Gong, Y., & de Lange, T. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.016 · Cited by 102 · see citing works
Expression of POT1 is Associated with Tumor Stage and Telomere Length in Gastric Carcinoma
Kondo, T., Oue, N., Yoshida, K., Mitani, Y., Naka, K., Nakayama, H., & Yasui, W. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1196 · Cited by 102 · see citing works
Proteasomes degrade proteins in focal subdomains of the human cell nucleus
Rockel, T. D., Stuhlmann, D., & von Mikecz, A. H. (2005) · Journal of Cell Science · doi:10.1242/jcs.02642 · Cited by 101 · see citing works
Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription
Diman, A., Boros, J., Poulain, F., Rodriguez, J., Purnelle, M., Episkopou, H., Bertrand, L., Francaux, M., Deldicque, L., & Decottignies, A. (2016) · Science Advances · doi:10.1126/sciadv.1600031 · Cited by 101 · see citing works
Self-citationStructural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer
Chen, C., Gu, P., Wu, J., Chen, X., Niu, S., Sun, H., Wu, L., Li, N., Peng, J., Shi, S., et al. (2017) · Nature Communications · doi:10.1038/ncomms14929 · Cited by 98 · see citing works
Regulation of USP7: A High Incidence of E3 Complexes
Kim, R. Q., & Sixma, T. K. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.05.028 · Cited by 97 · see citing works
Osterwald, S., Deeg, K. I., Chung, I., Parisotto, D., Wörz, S., Rohr, K., Erfle, H., & Rippe, K. (2015) · Journal of Cell Science · doi:10.1242/jcs.148296 · Cited by 92 · see citing works
Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML
Cao, T., Duprez, E., Borden, K. L. B., Freemont, P. S., & Etkin, L. D. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.10.1319 · Cited by 89 · see citing works
The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection.
Rai, R., Li, J.-M., Zheng, H., Lok, G. T.-M., Deng, Y., Huen, M. S.-Y., Chen, J., Jin, J., & Chang, S. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2172 · Cited by 88 · see citing works
Nicklas, S., Hillje, A., Okawa, S., Rudolph, I., Collmann, F. M., van Wuellen, T., del Sol, A., & Schwamborn, J. C. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0144-1 · Cited by 84 · see citing works
Bower, K., Napier, C. E., Cole, S. L., Dagg, R. A., Lau, L. M. S., Duncan, E. L., Moy, E. L., & Reddel, R. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050062 · Cited by 81 · see citing works
Young, J. A., Sermwittayawong, D., Kim, H., Nandu, S., An, N., Erdjument‐Bromage, H., Tempst, P., Coscoy, L., & Winoto, A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.172288 · Cited by 78 · see citing works
Physical and Functional Interactions between PML and MDM2
Wei, X., Yu, Z. K., Ramalingam, A., Grossman, S. R., Jiang, Y., Bloch, D. B., & Maki, C. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212215200 · Cited by 74 · see citing works
Tilman, G., Loriot, A. E., Beneden, A. V., Arnoult, N., Londoño‐Vallejo, A., Smet, C. D., & Decottignies, A. (2009) · Oncogene · doi:10.1038/onc.2009.23 · Cited by 62 · see citing works
Self-citationPost-translational modifications of PML: consequences and implications
Cheng, X., & Kao, H. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2012.00210 · Cited by 61 · see citing works
Dual-utility NLS drives RNF169-dependent DNA damage responses
An, L., Jiang, Y., Ng, H. H. W., Man, E. P. S., Chen, J., Khoo, U., Gong, Q., & Huen, M. S. Y. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616602114 · Cited by 60 · see citing works
Murine and human TSPYL genes: novel members of the TSPY-SET-NAP1L1 family
Vogel, T., Dittrich, O., Mehraein, Y., Dechend, F., Schnieders, F., & Schmidtke, J. (1998) · Cytogenetic and Genome Research · doi:10.1159/000015042 · Cited by 59 · see citing works
Sarkari, F., Wang, X., Nguyen, T., & Frappier, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016598 · Cited by 59 · see citing works
Frink, R. E., Peyton, M., Schiller, J. H., Gazdar, A. F., Shay, J. W., & Minna, J. D. (2016) · Oncotarget · doi:10.18632/oncotarget.9335 · Cited by 57 · see citing works
Highly Aggressive Metastatic Melanoma Cells Unable to Maintain Telomere Length
Viceconte, N., Dheur, M.-S., Majerová, E., Pierreux, C. E., Baurain, J., van Baren, N., & Decottignies, A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.046 · Cited by 56 · see citing works
Self-citationThe PML-Interacting Protein DAXX: Histone Loading Gets into the Picture
Salomoni, P. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00152 · Cited by 42 · see citing works
Gene silencing of TSPYL5 mediated by aberrant promoter methylation in gastric cancers
Jung, Y., Park, J., Bang, Y., & Kim, T.-Y. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700706 · Cited by 40 · see citing works
The Shelterin Component TPP1 Is a Binding Partner and Substrate for the Deubiquitinating Enzyme USP7
Zemp, I., & Lingner, J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.596056 · Cited by 29 · see citing works
Escoffier, E., Rezza, A., de Climens, A. R., Belleville, A., Gazzolo, L., Gilson, É., & Dodon, M. D. (2005) · Retrovirology · doi:10.1186/1742-4690-2-77 · Cited by 14 · see citing works
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Sun, H., Chen, G., Guo, B., Lv, S., & Yuan, G. (2023) · Journal of Cancer · doi:10.7150/jca.80097 · Cited by 11 · see citing works
Pinto, L., Baidarjad, H., Entz‐Werlé, N., & Dyck, E. V. (2021) · Cancers · doi:10.3390/cancers13225678 · Cited by 11 · see citing works
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Sharaf, R., Jin, D. X., Grady, J. P., Napier, C. E., Ebot, E. M., Frampton, G. M., Albacker, L. A., Thomas, D. M., & Montesion, M. (2023) · npj Genomic Medicine · doi:10.1038/s41525-023-00369-6 · Cited by 6 · see citing works
Dalui, S., Dasgupta, A., Adhikari, S., Das, C., & Roy, S. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102200 · Cited by 5 · see citing works
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Silonov, S. A., Smirnov, E. Y., Shmidt, E. A., Константинович, Т. К., Константинович, Т. К., & Fonin, A. V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010039 · Cited by 3 · see citing works
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Leng, X., Xie, S., Tao, D., Wang, Z., Shi, J., Yi, M., Tan, X., Zhang, X., Liu, Y., & Yang, Y. (2024) · Reproduction Fertility and Development · doi:10.1071/rd23042 · Cited by 3 · see citing works
SLFN11 restricts escape from telomere crisis to prevent alternative lengthening of telomeresPreprint
Segura‐Bayona, S., Borel, V., Stanage, T. H., Maric, M., Walter, M., Oliveira, R. A., Li, S., Idilli, A. I., Peritore, M., Hewitt, G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.10.675313 · Cited by 4 · see citing works
Wang, Z., Liu, Y., Zhang, Y., Shi, J., Xie, S., Yi, M., Zhang, X., Tao, D., & Yang, Y. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07694-x · Cited by 2 · see citing works
Specific death of ALT cells through TSPYL5 depletion
Claude, E., Episkopou, H., & Decottignies, A. (2019) · Molecular & Cellular Oncology · doi:10.1080/23723556.2019.1651603 · Cited by 2 · see citing works
Self-citationAncia, M., Wahni, K., Chakrowf, J., Aakchioui, A. E., Claude, E., de Lhoneux, G., Liberelle, M., Janvier, S., Baranova, E., Pueyo, J. M., et al. (2025) · Protein Science · doi:10.1002/pro.70116 · Cited by 1 · see citing works
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Silonov, S. A., Ведешкина, Е., Mokin, Y. I., Sukailo, D. A., Smirnov, E. Y., Reushev, V. A., Константинович, Т. К., Константинович, Т. К., & Fonin, A. V. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27094106 · Cited by 1 · see citing works
Constitutive cGAS-STING activation in ALT+ cellsPreprint
Geelen, D., Beacom, A., Vaurs, M., Mahieu, M., Boutoual, R., Derumier, A., Hoerr, R. E., Loriot, A. E., Nassour, J., & Decottignies, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.18.649516 · Cited by 1 · see citing works
Self-citationMahieu, M., Defour, J., Mathieu, B., Richiardone, E., Heremans, I. P., Fabiole, E., Levy, G., Berre, G. L., Scheers, I., Brichard, B., et al. (2025) · eLife · doi:10.1101/2025.06.27.661964
Self-citationSingle-stranded DNA-binding proteins at healthy and diseased telomeres
Lescalet, G., Monterroso, A. D. D., Kochman, R., Coulon, S., & Maréchal, A. (2026) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2025.11.010
Billard, P. (2021) · theses.fr (ABES) · doi:10.70675/7d145f6az2700z4c8bzad56z3286d493fb31
Coquette, C., Bouchoucha, K., Mahieu, M., Verleden, S. E., Loriot, A. E., Norris, K., Baird, D. M., Derumier, A., Hoton, D., Sadeleer, L. D., et al. (2026) · Aging Cell · doi:10.1111/acel.70512
Self-citationShi, J. H., Yi, M., Xie, S., Wang, Z., Zhang, X., Zhang, Y., Tang, R., Yang, Y., & Liu, Y. (2026) · Advanced Science · doi:10.1002/advs.202520273
Targeting USP7 in sarcomas: opportunities and challenges
Franzese, S., & Cassinelli, G. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118319
Fatima, S. U. K., Jabber, A., Khanam, M. H., Khan, J., Talukder, M. M., & Hasnat, M. A. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261476085
Wang, Y., & Shi, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1933967
Folini, M., Pasquali, S., & Zaffaroni, N. (2026) · Research Square · doi:10.21203/rs.3.rs-11116403/v1
- Authors
- Episkopou, H., Diman, A., Claude, E., Viceconte, N., & Decottignies, A.
- Affiliations
- de Duve Institute (BE)
- Corresponding author
- Decottignies, Anabelle
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 75
- Issue
- 3
- Pages
- 469-482.e6
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2954024809
- Cited by
- 55
- References
- 55
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 3 · 2023: 12 · 2022: 4 · 2021: 9 · 2020: 9 · 2019: 2
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds National de la Recherche Scientifique-Télévie (7.4517.15, 7.6504.16, 7.4519.18)
- FNRS
- de Duve Institute
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- TSPYL5, alternative lengthening of telomeres, POT1, USP7, proteasomal degradation, polyubiquitination, PML bodies, shelterin, telomere maintenance, E3 ubiquitin ligase, cancer therapy targets, cell death
- MeSH terms
- Promyelocytic Leukemia Protein, Ubiquitin-Specific Peptidase 7, Shelterin Complex, Cell Line, Cell Survival, Humans, Neoplasms, Nuclear Proteins, Protein Binding, Telomere, Telomere-Binding Proteins, Ubiquitin-Protein Ligases, Ubiquitination, Telomere Homeostasis, Proteolysis
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